How Can Keratins Influence Toxic Cell Injury?
Keratins were shown to undergo extensive modifications in various cell culture and in vivo conditions. They include phosphorylation, ubiquitination, proteolytic cleavage, and cross linking, which modulate the status of the keratin IF cytoskeleton and the interaction of keratins with several cellular proteins, particularly signaling molecules.35,54,60,61 K8 and 18 are substrates of a variety of protein kinases involved in mitosis, apoptosis and stress.35 Antibodies directed against specific phosphoepitopes on keratin revealed that K8 and 18 become phosphorylated at many sites in human ASH as well as in DDC-fed mice.62 Some of these phosphorylation sites were targets of stress-induced protein kinases and were phosphorylated already within one day of intoxication. This indicates that phosphorylation of keratin might be one of the initial mechanisms of involving keratins in toxic stress responses. A direct role of keratin phosphorylation as modulator of cell toxicity was demonstrated in tr
